Abstract
Exposure to estrogen-mimicking chemicals during critical periods of development, such as infancy, may have adverse effects. However, these effects can be difficult to characterize in most epidemiologic studies. For example, growth of reproductive organs may be susceptible to estrogenic chemicals, but measuring it requires skilled ultrasound examination; timing of pubertal onset may be altered, but observing it requires long-term follow up. To address the need for a simple marker of response to estrogenic exposures in infants, we propose a novel application of a classic marker of estrogen response in adult women: cytological evaluation of urogenital epithelial cells. In this cross-sectional study of 34 female and 41 male infants, we demonstrate that epithelial cells can be obtained from swabs of the vaginal introitus (females) and urethral meatus (males), as well as from spun urine, and that these cells respond to differential estrogenic conditions, as indicated by the relative abundance of the superficial epithelial cell type. To model varying estrogen exposure, we sampled from infants who were either newborn (highly exposed to maternal estrogens), or 12 weeks old (12W) (negligibly exposed to estrogen). Newborns had a higher percentage of superficial cells (%S), as compared to 12W (mean ± standard error: 8.3 ± 1.8 vs. 0.9 ± 0.2) (p < 0.01), consistent with an estrogen response. This difference in %S from newborn to 12W was observed similarly for swab (-7.6 ± 1.7) and urine (-7.3 ± 2.6) specimens and for males (-9.6 ± 2.9) and females (-5.2 ± 2.1). Examination of urogenital epithelial cells can successfully demonstrate estrogen response in both sexes, using cell specimens collected from either swab or urine sampling. In future studies, this simple, non-invasive method may be applied to assess whether estrogen-mimicking chemicals produce an estrogenic response in infants.
Highlights
The endocrine disruption hypothesis states that hormonally active pollutant chemicals are interfering with endocrine function in the general population
We have shown that the uterus and male breast are large at birth, consistent with the known trophic effect of maternal estrogen, and that these organs shrink as the infant gets older and estrogen exposure is lost [2]
Of 141 processed specimens representing 75 infants, 94 specimens, representing 58 infants were successfully scored by the National Institute of Environmental Health Sciences (NIEHS) Pathologist (66%, 36 complete swab-urine pairs) (Table 1)
Summary
The endocrine disruption hypothesis states that hormonally active pollutant chemicals are interfering with endocrine function in the general population. Estrogen-mimicking compounds are perhaps the best studied of the endocrine disrupting chemicals. Exposure to these chemicals during critical periods of development, such as infancy, is of particular concern. Reproductive organ volume may be a useful measure for evaluating whether an infant is responding to a biologically relevant amount of a substance with estrogenic activity. These measures, are technically challenging to obtain--for example, evaluating the uterus requires ultrasound, and breast tissue can be difficult to distinguish from fat
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